Adam Teut
Development Pathways Paper
BIO 351
13-Mar-09
The Beat of Life- development of the heart
Ba-dub, ba-dub. In the left side of a normal human’s chest in a fist sized lump named the heart. The lump composed of muscular cardial and nephrocytic pericardial cells which at the whim of a pulse of electrical current coursing through various nodes causing it to constrict and relax pumping newly oxygenated blood throughout the body. How does such a miraculous organ emerge from a fertilized egg?
Heart development is triggered by signaling molecules and is guided by certain transcription factors which are tissue-specific. Activation of the genes causes development to begin. Cardiomyocytes or cardiac muscle cells generate anterior of the lateral mesoderm after gastulation. This occurs as the response from bone morphogenetic proteins which come from the endosperm. This activates the expression of the Nkx2.5 gene, a molecular marker for cardiac lineage. Nkx2.5 works with zinc-finger transcription factors from GATA family to activate the cardiac gene expression.
The cardiac muscle cells, now marked for specification, come together in a mass forming a lateral heart tube along the ventral midline of the embryo. The heart tube has now separate myocardial and endocardial layers divided by an extracellular matrix. The tube goes through a right-ward looping for reasons yet to be determined, but the direction is controlled in the same way with the same asymmetric signaling system which aligns other internal organs. Ptx2, a transcription factor, is expressed on the left side of the heart as it interprets the left-right signaling. Also, Sonic hedgehog and Nodal are expressed asymmetrical in the lateral mesoderm.
Cells of the heart seemed to be fated to form chambers sometime during looping before the chambers are formed similar to the way the lateral tube was formed. The heart tube is patterned into segments predetermined as various parts of the heart to be formed. Although how chambers are identified is unknown, it may involve a certain array of transcriptional factors. As coronary arteries develop, Cardiomyocytes specified for ventricle formation distinguish as endothelin-1 of ET-1 signals through the cells to cause the formation of the conduction system which controls heartbeat.
Ventricles need dHand and Nkx2.5 genes to expression of the Irx4 gene which is found to be ventricle-specific homeobox gene.
For Atria have COUP-TFII, an orphan nuclear receptor, expressed in their precursory cells and require it for growth.
Growth of the heart occurs as cardiomyocytes increase in order to hold the haemodynamic load as the embryo develops. The endocardium releases neuregulin growth factors recognized by ErbB2 and ErbB4 receptors allow for the development of the trabeculae.
Cardiac Valves are placed to allow for the division of the four chambers of the developed heart. This formation is what ensures the flow of blood is unidirectional. The chambers are formed from a single cardiac tube via the swelling of the extracellular fluid between the two layers in specific spots. Theses spots referred to as cardiac go on in development to form the basis of cells from which the atrioventricular and ventriculoarterial valves form. Reciprocal signaling in-between the layers specifically in the cushion regions transform endocardial cells to mesenchymal cells, a type of stem cell, which become the fibrous tissue composing the valves. Neural crest cells allow for the sepation of the arteries and formation of the connecting vessels.
*note this is the basics of heart development. I need to expand on the genetics and mechanisms of the whole process.
Olson, Eric and Srivastava, Deepak. “A Genetic Blueprint for Cardiac Development”. NATURE. Vol 407. 14 September 2000.
